Platelets, von Willebrand factor, and prostaglandin I2.
Depending on the time of addition, prostaglandin I2 (PGI2; greater than or equal to 10(-9) M) either inhibits or reverses platelet agglutination mediated by human factor VIII-related von Willebrand factor activity (FVIIIvWF) and ristocetin, or bovine FVIIIvWF alone. 6-Keto-PGF1 alpha, the inactive metabolite of PGI2, is without effect, PGI2 inhibition is potentiated by the phosphodiesterase inhibitor, theophylline, and is not the result of PGI2 suppression of ADP release. PGI2 (+/- theophylline) does not inhibit ristocetin-induced binding of purified human 125I-FVIIIvWF multimers to washed platelets or to platelets treated with PGI2 and then formalin fixed (although subsequent agglutination of these platelets is impaired). Washed platelets treated previously with 2-aminoethylisothiouronium bromide (AET), an agent that reduces disulfide bonds and alters platelet membranes, also bind human 125I-FVIIIvWF multimers without agglutinating. We conclude that FVIIIvWF-mediated agglutination requires both functional platelet FVIIIvWF binding sites and platelet-platelet cohesion sites, and that platelet surface cohesion sites are altered by AET and PGI2. PGI2 from adjacent intact endothelial cells may prevent excessive platelet accumulation on exposed subendothelium without suppressing an essential hemostatic process--the binding of platelets to subendothelial FVIIIvWF.
D000818:Animals; D001779:Blood Coagulation Factors / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005169:Factor VIII / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*; D011485:Protein Binding; D013806:Theophylline / Q000494:pharmacology; D014841:von Willebrand Factor / Q000502:physiology*
D001779:Blood Coagulation Factors; D011453:Prostaglandins; D014841:von Willebrand Factor; D005169:Factor VIII; D013806:Theophylline; D011464:Epoprostenol